A method for efficiently preparing a cymene ruthenium diiodide dimer

Abstract

This invention discloses an efficient method for preparing p-cymene ruthenium iodide dimer. The method uses ruthenium trichloride as the ruthenium source, propylterpinene as the ligand precursor, and an alcohol solvent as the reaction medium. The target product is synthesized efficiently through a two-step continuous reaction. First, ruthenium trichloride and propylterpinene are reacted at a specific temperature to generate a dichloro(p-cymene)ruthenium dimer intermediate. Then, an iodide aqueous solution is added for reflux reaction to complete the replacement of chloride ions with iodide ions. Finally, high-purity p-cymene ruthenium iodide dimer is obtained after simple post-processing. This invention innovatively uses propylterpinene instead of traditional phellandrene, significantly improving the stability and purity of the raw materials and reducing production costs. The one-step integrated process simplifies the operation process, avoids the risk of organic vapor exposure, and improves production safety. Optimized reaction parameters and material ratios achieve a product yield of up to 99.8%, and the process is adaptable to large-scale production requirements.

Description

Technical Field

[0001] This invention relates to the field of asymmetric hydrogenation catalyst preparation technology, specifically to a highly efficient method for preparing ruthenium iodide dimers of cymenes, which is particularly suitable for the industrial production of key catalysts in scenarios such as pharmaceutical intermediate synthesis, asymmetric catalytic reactions, CH bond activation, and cross-coupling reactions. Background Technology

[0002] Ruthenium diiodide dimer, chemically known as diiodine (p-cymene)ruthenium dimer, is a high-performance transition metal catalyst. Its unique molecular structure and electronic properties exhibit high activity and selectivity in catalytic reactions, making it one of the core catalysts in the field of asymmetric synthesis.

[0003] In the field of pharmaceutical synthesis, this catalyst, as an asymmetric hydrogenation catalyst, can significantly improve the synthesis yield and stereoselectivity of important pharmaceutical intermediates such as sacuribtriol intermediates. Sacuribtriol, as a key drug component for treating heart failure, places extremely high demands on catalyst performance during its synthesis. The application of ruthenium iodide dimer for cymene can effectively reduce byproduct formation, improve product purity, and lower pharmaceutical production costs.

[0004] In the field of organic synthesis, ruthenium iodide dimers of p-cymenes exhibit outstanding performance in enantioselective catalytic reactions of ketones and alkenes, efficiently enabling the construction of chiral centers and providing a reliable route for the synthesis of chiral compounds. Furthermore, this catalyst can also serve as a precatalyst for CH bond activation and cross-coupling reactions, and is a key precursor material for the synthesis of other advanced ruthenium catalysts, holding an irreplaceable position in the organic synthesis industry chain.

[0005] With the rapid development of industries such as pharmaceuticals and fine chemicals, the market demand for high-purity, low-cost p-cymene ruthenium iodide dimers continues to grow. However, existing preparation technologies have many shortcomings, limiting their industrial application.

[0006] A prior art method for preparing diiodine (p-cymene)ruthenium dimer uses dichloro-p-cymene ruthenium dimer as a raw material. First, the dichloro-p-cymene ruthenium dimer is dissolved in dichloromethane solvent. Then, an aqueous solution of iodide is added to carry out an ion-displacement reaction. Finally, the product is obtained through post-processing purification methods such as filtration, extraction, separation, and drying. This process is a heterogeneous reaction, and water and dichloromethane have extremely poor compatibility, resulting in a long reaction time. Furthermore, dichloromethane has high volatility and physiological toxicity. Other reported synthesis processes also generally suffer from the following problems: Poor raw material stability and high cost: Existing processes mostly use phellandrene as a ligand precursor. Phellandrene is a natural extract, and its purity is greatly affected by factors such as the source of raw materials and extraction process, making it difficult to maintain a high purity level. This results in significant quality differences between batches of products. At the same time, the preparation cost of natural extracts is high, which increases the production cost of the target product.

[0007] Low production safety: Existing processes require multiple steps such as filtration, redispersion, extraction, and separation, which involve the volatilization of large amounts of organic gases. These gases not only have a pungent odor but also pose safety hazards such as combustion and explosion, seriously threatening the health of operators and the production environment.

[0008] Complex process and low yield: Existing processes usually require two separation processes, which are cumbersome and result in significant product loss during separation, leading to a low final product yield, generally between 70% and 80%, which is difficult to meet the efficiency requirements of large-scale industrial production.

[0009] Significant environmental pressure: Some processes use toxic and harmful organic solvents, and the subsequent separation and purification processes generate a large amount of waste liquid and waste residue, which are difficult to treat and have high environmental protection costs, which is not in line with the development trend of green chemical industry.

[0010] Therefore, developing a method for preparing p-cymene ruthenium iodide dimer that uses stable raw materials, has low cost, simple process, is safe and environmentally friendly, and has a high yield has become an urgent technical problem to be solved in this field. Summary of the Invention

[0011] The purpose of this invention is to overcome the shortcomings of the prior art and provide an efficient method for preparing ruthenium iodide dimer of cymene. This method solves the problems of unstable raw materials, high cost, low safety and low yield in the prior art by innovative raw material selection, optimized process parameters and process design, so as to achieve efficient, safe and large-scale production of the target product.

[0012] To achieve the above objectives, the present invention provides the following technical solution: a highly efficient method for preparing ruthenium iodide dimer of cymene, comprising the following steps: Step (1): Disperse ruthenium trichloride and propylterpinene sequentially in an alcohol solvent and react at 75~120℃ for 1~4h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer; Step (2): Add an aqueous solution of iodide to the reaction solution obtained in step (1), heat and reflux for 4-12 hours, and obtain ruthenium iodide dimer of p-cymene after post-treatment.

[0013] Preferably, in step (1), the purity of propylterpinene is ≥95%, preferably 98%~99.5%.

[0014] Preferably, in step (1), the alcohol solvent is selected from one or more of methanol, ethanol, propanol, and isopropanol, and is preferably anhydrous ethanol or isopropanol.

[0015] Preferably, in step (1), the mass-volume ratio of ruthenium trichloride, terpinene propylene and alcohol solvent is 1.5~3.4g:15~40ml:50~100ml, more preferably 1.4~2.8g:13~31ml:45~84ml, and even more preferably 1.8g:18ml:56ml.

[0016] Preferably, in step (2), the iodide is selected from hydroiodic acid, sodium iodide, potassium iodide, and calcium iodide, with potassium iodide being the most preferred.

[0017] Preferably, in step (2), the mass-to-volume ratio of ruthenium trichloride, iodide and water is 1:1.3~3.0g:10~30ml, more preferably 1:1.3~2g:10~20ml, and even more preferably 1:1.5g:15ml.

[0018] Preferably, in step (2), the heating temperature of the reflux reaction is 70~120℃, more preferably 75~95℃, and even more preferably 90~100℃; the reaction time is preferably 2~3h, and even more preferably 3h.

[0019] Preferably, in step (1), the reaction system is carried out under nitrogen protection, and the number of nitrogen replacements is 2 to 5 times, preferably 3 times.

[0020] Preferably, in step (1), the ruthenium content in the raw material ruthenium trichloride is 30%~40%, preferably 37%.

[0021] Preferably, the post-processing includes the following steps: cooling the system after the reaction in step (2) to 20~30℃, filtering and collecting the solid product, washing it with deionized water 2~4 times and methanol 1~3 times in sequence, and then drying it at 60~80℃ for 4~8h to obtain p-cymene ruthenium iodide dimer; The amount of deionized water used in a single wash is 1 / 5 to 1 / 3 of the total volume of the reaction system, and the amount of methanol used in a single wash is 1 / 10 to 1 / 5 of the total volume of the reaction system.

[0022] The preparation method of the present invention has the following beneficial effects: (1) Significant advantages in raw materials: The use of propyl terpinene to replace traditional phellandrene ensures a stable purity of ≥95%, guaranteeing consistent product quality; the cost of chemically synthesized raw materials is 30%~50% lower than that of natural extracts, greatly enhancing the market competitiveness of the product.

[0023] (2) Simple and efficient process: Through a two-step continuous reaction integrated process, no intermediate separation steps are required, simplifying the operation process and shortening the production cycle to 5~16h, which is more than 40% shorter than the traditional process; the product yield in ruthenium can reach 85%~99.8%, and the purity is ≥98%, which is far higher than the existing technology level.

[0024] (3) Safety and environmental protection: Low-toxicity alcohol solvents are used to avoid the use of toxic and harmful reagents; the reaction process does not require multiple filtrations and redispersions, reducing the risk of organic vapor exposure and significantly improving operational safety; the waste liquid generated in the post-treatment can be recovered by simple distillation, resulting in less waste residue and less environmental pressure.

[0025] (4) Strong adaptability to scale: The process is simple to operate and the parameters are easy to control. It can be directly scaled up from the laboratory scale to the industrial production scale. When the amount of ruthenium trichloride is 1000g, the product yield can still reach 99.8%, which meets the needs of large-scale industrial production.

[0026] The above description is merely an overview of the technical solutions of the embodiments of this application. In order to better understand the technical means of the embodiments of this application and to implement them in accordance with the contents of the specification, and to make the above and other objects, features and advantages of the embodiments of this application more apparent and understandable, specific implementation methods of this application are described below. Attached Figure Description

[0027] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0028] Figure 1 This is a process flow diagram of the present invention; Figure 2 This is a schematic diagram of the HPLC chromatogram of the present invention; Figure 3 This is the infrared spectrum of the present invention; Figure 4 This is the X-ray diffraction pattern of the present invention. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0030] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains; the terminology used herein in the specification of the application is for the purpose of describing particular embodiments only and is not intended to limit the application; the terms “comprising” and “having”, and any variations thereof, in the specification, claims and drawings of this application are intended to cover non-exclusive inclusion.

[0031] The term "embodiment" as used herein means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of the phrase "embodiment" in various places throughout the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0032] Furthermore, the terms "first," "second," etc., in the specification and claims of this application or in the aforementioned drawings are used to distinguish different objects rather than to describe a specific order, and may explicitly or implicitly include one or more of the features.

[0033] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, "connection" or "joining" in mechanical structures can refer to a physical connection, such as a fixed connection, for example, a connection fixed by fasteners, such as a connection fixed by screws, bolts, or other fasteners; a physical connection can also be a detachable connection, such as a snap-fit ​​or interlocking connection; a physical connection can also be an integral connection, such as a connection formed by welding, bonding, or integral molding. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0034] To enable those skilled in the art to better understand the present application, the following will be combined with... Figures 1-4 The technical solutions in the embodiments of this application will be clearly and completely described.

[0035] A highly efficient method for preparing ruthenium iodide dimer of cymene includes the following steps: Step (1): Intermediate synthesis Ruthenium trichloride and terpinene were sequentially dispersed in an alcohol solvent and reacted at 75-120°C for 1-4 hours under nitrogen protection to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0036] In this step, propylterpinene, chemically known as 1-isopropyl-4-methyl-1,4-cyclohexadiene, serves as a ligand precursor and is characterized by structural stability and easily controllable purity. Compared to traditional phellandrene, propylterpinene can be prepared on a large scale through chemical synthesis, achieving a stable purity of over 95%, preferably 98%~99.5%, effectively ensuring reaction stability and product quality consistency. Furthermore, the production cost of chemically synthesized propylterpinene is significantly lower than that of naturally extracted phellandrene, substantially reducing the preparation cost of the target product.

[0037] The alcohol solvent is selected from one or more of methanol, ethanol, propanol, and isopropanol, preferably anhydrous ethanol or isopropanol. This type of solvent has the characteristics of good solubility, low toxicity, and easy recovery, enabling ruthenium trichloride and propylterpinene to be fully dispersed and reacted, while reducing the difficulty of subsequent separation and processing. The mass-volume ratio of ruthenium trichloride, propylterpinene, and alcohol solvent is 1.5~3.4g:15~40ml:50~100ml, preferably 1.4~2.8g:13~31ml:45~84ml, and more preferably 1.8g:18ml:56ml. This ratio ensures complete reaction of the raw materials and avoids cost waste or incomplete reaction due to excessive amounts of any one raw material.

[0038] The reaction temperature is controlled between 75 and 120°C. This temperature range activates the reaction system, promotes the coordination reaction between ruthenium trichloride and propylterpinene, and avoids excessively high temperatures that could lead to raw material decomposition or exacerbate side reactions. The reaction time is 1 to 4 hours to ensure the full formation of the intermediate dichloro(p-cymene)ruthenium dimer. Furthermore, the reaction is carried out under nitrogen protection, with 2 to 5 nitrogen purging cycles, preferably 3, to effectively isolate oxygen, prevent the oxidation of ruthenium ions, and improve reaction selectivity.

[0039] Step (2): Ion substitution and product formation Add an aqueous solution of iodide to the reaction solution obtained in step (1), heat to 70~120℃ and reflux for 4~12h. After the reaction is completed, post-treatment is performed to obtain ruthenium iodide dimer of p-cymene.

[0040] In this step, iodide serves as the source of iodide ions, selected from hydroiodic acid, sodium iodide, potassium iodide, and calcium iodide, with potassium iodide being preferred. Potassium iodide has the advantages of good solubility, high reactivity, and low cost, and can rapidly undergo an ion substitution reaction with the intermediate dichlororuthenium dimer, replacing chloride ions with iodide ions to generate the target product.

[0041] The mass-to-volume ratio of ruthenium trichloride, iodide, and water is 1:1.3~3.0g:10~30ml, preferably 1:1.3~2g:10~20ml, and more preferably 1:1.5g:15ml. This ratio ensures an excess of iodide ions, promotes complete ion exchange reaction, and improves product yield. The reflux reaction temperature is 70~120℃, preferably 75~95℃, and more preferably 90~100℃; the reaction time is preferably 2~3h, and more preferably 3h. A suitable combination of temperature and time can accelerate the reaction rate while avoiding product decomposition, ensuring reaction efficiency and product quality.

[0042] Post-processing includes cooling, filtration, washing, and drying: After the reaction, the system is naturally cooled to 20-30°C, and the solid product is collected by filtration; the system is washed 2-4 times with deionized water to remove soluble salt impurities, with the amount of deionized water used in each wash being 1 / 5 to 1 / 3 of the total volume of the reaction system; the system is then washed 1-3 times with methanol to remove residual organic solvents and unreacted raw materials, with the amount of methanol used in each wash being 1 / 10 to 1 / 5 of the total volume of the reaction system; finally, the washed solid product is dried at 60-80°C for 4-8 hours to obtain a purplish-black ruthenium iodide dimer powder. Example 1

[0043] This embodiment provides an efficient method for preparing ruthenium iodide dimers of cymene, the specific steps of which are as follows: Intermediate synthesis: 1.8 g of ruthenium trichloride (Ru content 37%) was dispersed in 56 ml of isopropanol and stirred for 10 min until completely dissolved. 18 ml of propylterpinene (purity 99%) was added to the reaction system, nitrogen was purged 3 times, and the reaction was carried out at 90 °C for 3 h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0044] Ion substitution and product formation: Add 30 ml of 2.7 g sodium iodide aqueous solution to the above reaction solution and continue to reflux at 90 °C for 4 h.

[0045] Post-processing: The reaction system was cooled to 25°C, the solid product was collected by filtration, washed three times with deionized water (20 ml each time), and then washed twice with methanol (10 ml each time). The solid product was dried at 70°C for 6 h to obtain 2.82 g of purplish-black ruthenium iodide dimer powder.

[0046] Product testing: The purity of the product was 98.2% as determined by high performance liquid chromatography (HPLC); the yield was 88% based on ruthenium. Example 2

[0047] This embodiment provides an efficient method for preparing ruthenium iodide dimers of cymene, the specific steps of which are as follows: Intermediate synthesis: 1.8 g of ruthenium trichloride (Ru content 37%) was dispersed in 56 ml of anhydrous ethanol and stirred for 10 min until completely dissolved. 18 ml of propylterpinene (purity 99.5%) was added to the reaction system, nitrogen was purged 3 times, and the reaction was carried out at 90 °C for 3 h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0048] Ion substitution and product formation: Add 27 ml of 2.7 g potassium iodide aqueous solution to the above reaction solution and continue to reflux at 90 °C for 4 h.

[0049] Post-processing: The reaction system was cooled to 22°C, the solid product was collected by filtration, washed three times with deionized water (18 ml each time), and then washed twice with methanol (8 ml each time). The solid product was dried at 65°C for 5 h to obtain 3.16 g of purplish-black ruthenium iodide dimer powder.

[0050] Product testing: HPLC analysis showed that the product purity was 99.1% and the yield based on ruthenium was 98.8%. Example 3

[0051] This embodiment provides a method for large-scale production of p-cymene ruthenium iodide dimer, the specific steps of which are as follows: Intermediate synthesis: 200g of ruthenium trichloride (Ru content 37%) was dispersed in 6300ml of anhydrous ethanol and stirred for 15min until completely dissolved. 200ml of propylterpinene (purity 99.2%) was added to the reaction system, nitrogen gas was purged 3 times, and the reaction was carried out at 90℃ for 3h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0052] Ion substitution and product formation: Add 300g of potassium iodide in 3000ml of aqueous solution to the above reaction solution and continue to reflux at 90℃ for 4h.

[0053] Post-processing: The reaction system was cooled to 28°C, the solid product was collected by filtration, washed 4 times with deionized water (1500 ml each time), and then washed 3 times with methanol (600 ml each time). The solid product was dried at 75°C for 7 h to obtain 353 g of purplish-black ruthenium iodide dimer powder.

[0054] Product testing: HPLC analysis showed that the product purity was 99.3% and the yield based on ruthenium was 99.2%. Example 4

[0055] This embodiment provides a method for large-scale industrial production of ruthenium iodide dimer for p-cymene, the specific steps of which are as follows: Intermediate synthesis: 1000g of ruthenium trichloride (Ru content 37%) was dispersed in 31800ml of anhydrous ethanol and stirred for 15min until completely dissolved. 11500ml of propylterpinene (purity 99.5%) was added to the reaction system, nitrogen was purged 3 times, and the reaction was refluxed at 90℃ for 3h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0056] Ion substitution and product formation: Add 13900 ml of 1500 g potassium iodide aqueous solution to the above reaction solution and continue the reaction at 100 °C for 6 h.

[0057] Post-processing: The reaction system was cooled to 25°C, the solid product was collected by filtration, washed 4 times with deionized water (8000 ml each time), and then washed 3 times with methanol (3000 ml each time). The solid product was dried at 80°C for 8 hours to obtain 1775.2 g of purplish-black ruthenium iodide dimer powder.

[0058] Product testing: HPLC analysis showed that the product purity was 99.5% and the yield based on ruthenium was 99.8%. Example 5

[0059] This embodiment provides an efficient method for preparing ruthenium iodide dimers of cymene, the specific steps of which are as follows: Intermediate synthesis: 2.5 g of ruthenium trichloride (Ru content 37%) was dispersed in 80 ml of methanol and stirred for 12 min until completely dissolved. 30 ml of propylterpinene (purity 95%) was added to the reaction system, nitrogen was purged 4 times, and the reaction was carried out at 100 °C for 2 h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0060] Ion substitution and product formation: Add 25 ml of 5.0 g calcium iodide aqueous solution to the above reaction solution and continue to reflux at 85 °C for 3 h.

[0061] Post-processing: The reaction system was cooled to 24°C, the solid product was collected by filtration, washed three times with deionized water (30 ml each time), and then washed twice with methanol (15 ml each time). The solid product was dried at 68°C for 5 h to obtain 4.12 g of purplish-black ruthenium iodide dimer powder.

[0062] Product testing: HPLC analysis showed that the product purity was 98.5% and the yield based on ruthenium was 92.3%. Example 6

[0063] This embodiment provides an efficient method for preparing ruthenium iodide dimers of cymene, the specific steps of which are as follows: Intermediate synthesis: 1.4 g of ruthenium trichloride (Ru content 37%) was dispersed in 45 ml of propanol and stirred for 8 min until completely dissolved. 13 ml of propylterpinene (purity 98%) was added to the reaction system, nitrogen was purged twice, and the reaction was carried out at 75 °C for 4 h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer.

[0064] Ion substitution and product formation: Add 10 ml of aqueous solution of 1.8 g hydroiodic acid to the above reaction solution and continue to reflux at 75 °C for 5 h.

[0065] Post-processing: The reaction system was cooled to 20°C, the solid product was collected by filtration, washed twice with deionized water (15 ml each time), and then washed once with methanol (8 ml each time). The solid product was dried at 60°C for 4 h to obtain 2.21 g of purplish-black ruthenium iodide dimer powder.

[0066] Product testing: HPLC analysis showed that the product purity was 98.0% and the yield based on ruthenium was 85.7%.

[0067] Comparative Example 1 The specific steps for preparing p-cymene ruthenium iodide dimer using existing techniques are as follows: 1.8 g of ruthenium trichloride (Ru content 37%) and 18 ml of phellandrene (purity 85%) were dissolved in 56 ml of anhydrous ethanol, nitrogen was purged three times, and the reaction was refluxed at 80 °C for 4 h. After cooling and filtration, orange-red dichloro-p-cymene ruthenium dimer was obtained.

[0068] Dichloro-p-cymene ruthenium dimer was dissolved in 40 ml of dichloromethane, and an aqueous solution (20 ml) containing 2.7 g of potassium iodide was added. The mixture was stirred vigorously under nitrogen for 15 h. The mixture was extracted and separated, and the dichloromethane phase was collected. The aqueous phase was washed three times with dichloromethane until the dichloromethane phase was colorless. The dichloromethane phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under reduced pressure to obtain 1.98 g of p-cymene ruthenium iodide dimer powder.

[0069] Product testing: HPLC analysis showed that the product purity was 95.3% and the yield based on ruthenium was 61.5%.

[0070] Performance Comparison Analysis The preparation process and product performance of Examples 1-4 of the present invention were compared with those of Comparative Example 1, and the results are shown in Table 1: ligand precursor Propylterpinene (99% purity) Propylterpinene (purity 99.5%) Propylterpinene (purity 99.2%) Propylterpinene (purity 99.5%) Phyllanthrene (85% purity) solvent Isopropanol Anhydrous ethanol Anhydrous ethanol Anhydrous ethanol dichloromethane Reaction steps Continuous reaction Continuous reaction Continuous reaction Continuous reaction 2-step reaction Production cycle 8h 8h 8h 12h 24h Product purity 98.2% 99.1% 99.3% 99.5% 95.3% Yield (in ruthenium) 88% 98.8% 99.2% 99.8% 61.5% Raw material costs (relative value) 70 70 65 60 100 As shown in the table above, the preparation method of the present invention has the following significant advantages compared with the prior art: Higher purity of raw materials: The purity of propylterpinene is ≥95%, which is much higher than that of phellandrene (85%), ensuring the high purity of the product.

[0071] The process is simpler: a two-step continuous reaction replaces a multi-step reaction, eliminating the need for complex purification steps such as extraction and separation, and vacuum rotary evaporation, thus shortening the production cycle by more than 60%.

[0072] Superior product performance: Product purity ≥98%, an improvement of 3-4 percentage points compared to existing technologies; Yield ≥88%, reaching up to 99.8%, an improvement of more than 26.5 percentage points compared to existing technologies.

[0073] Lower costs: Raw material costs are reduced by 30% to 40%, and no complex separation equipment is required, further reducing the overall cost of industrial production.

[0074] In this invention, the ruthenium content of ruthenium trichloride can be adjusted within the range of 30% to 40%, preferably 37%. Ruthenium trichloride within this content range is readily available on the market and ensures efficient reaction. If the ruthenium content is below 30%, the feed amount needs to be increased to ensure a sufficient supply of ruthenium ions; if the ruthenium content is above 40%, it may lead to an increase in the impurity content in the reaction system, affecting the purity of the product. The purity of propylterpinene is ≥95%. If the purity is below 95%, it needs to be purified by distillation before use; otherwise, excessive impurities will lead to an aggravation of side reactions, resulting in a decrease in product yield and purity. The alcohol solvent can be selected as a single solvent or a mixed solvent according to actual production needs. The ratio of the mixed solvent can be adjusted according to the solubility of the raw materials and the reaction rate. For example, using methanol and ethanol in a 1:1 ratio can further improve the solubility of the raw materials. The choice of iodide should be based on a comprehensive consideration of cost and reaction effect. Potassium iodide has the highest reactivity and cost-effectiveness, making it the preferred option. Hydroiodic acid has high reactivity but is highly corrosive, requiring corrosion-resistant equipment. Sodium iodide and calcium iodide react slightly less effectively than potassium iodide, but can still be used in specific scenarios. Reaction temperature and time can be adjusted appropriately according to the reaction scale. For small-scale experiments (feed amount < 5g), the reaction time can be shortened; for large-scale production (feed amount > 100g), the reaction time can be extended to ensure complete reaction. During post-processing, the number of washes and the amount used can be adjusted according to the required product purity. If the product purity does not meet the requirements, the number of washes or the amount used can be increased. Drying temperature and time must be strictly controlled to avoid product decomposition due to excessively high temperature, and excessively high moisture content due to excessively low temperature or short drying time.

[0075] The present invention provides an efficient method for preparing p-cymene ruthenium iodide dimer, overcoming many technical deficiencies in existing technologies and possessing significant technical advantages and economic value. The product prepared by this method has high purity and high yield, and can be widely applied in the synthesis of pharmaceutical intermediates, asymmetric catalytic reactions, CH bond activation, and cross-coupling reactions, especially suitable for the industrial production of important pharmaceutical products such as sacurbit intermediates.

[0076] Meanwhile, this method is simple, safe, environmentally friendly, and low-cost, enabling large-scale production and meeting the market demand for high-purity ruthenium iodide dimers. Furthermore, the core innovations of this method (the application of propylterpinene and the two-step continuous reaction process) can provide a reference for the preparation of other transition metal catalysts, possessing significant value for technology promotion.

[0077] In summary, the efficient preparation method of p-cymene ruthenium iodide dimer of the present invention is innovative and advanced in technology, cost-effective in economics, in line with the trend of green chemical development in the environment, and has the prospect of large-scale industrial application. It can bring important technological breakthroughs and industrial upgrading to the field of asymmetric hydrogenation catalyst preparation technology.

[0078] The above-described embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.

Claims

1. A highly efficient method for preparing ruthenium iodide dimer of cymene, characterized in that: Includes the following steps: Step (1): Disperse ruthenium trichloride and propylterpinene sequentially in an alcohol solvent and react at 75~120℃ for 1~4h to obtain a reaction solution containing dichloro(p-cymene)ruthenium dimer; Step (2): Add an aqueous solution of iodide to the reaction solution obtained in step (1), heat and reflux for 4-12 hours, and obtain ruthenium iodide dimer of p-cymene after post-treatment.

2. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (1), the purity of propylterpinene is ≥95%, preferably 98%~99.5%.

3. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (1), the alcohol solvent is selected from one or more of methanol, ethanol, propanol, and isopropanol, preferably anhydrous ethanol or isopropanol.

4. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (1), the mass-volume ratio of ruthenium trichloride, terpinene propylene, and alcohol solvent is 1.5~3.4g:15~40ml:50~100ml, preferably 1.4~2.8g:13~31ml:45~84ml, and more preferably 1.8g:18ml:56ml.

5. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (2), the iodide is selected from hydroiodic acid, sodium iodide, potassium iodide, and calcium iodide, preferably potassium iodide.

6. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (2), the mass-volume ratio of ruthenium trichloride, iodide and water is 1:1.3~3.0g:10~30ml, preferably 1:1.3~2g:10~20ml, and more preferably 1:1.5g:15ml.

7. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (2), the heating temperature of the reflux reaction is 70~120℃, preferably 75~95℃, more preferably 90~100℃; the reaction time is preferably 2~3h, more preferably 3h.

8. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (1), the reaction system is carried out under nitrogen protection, and the nitrogen is replaced 2 to 5 times, preferably 3 times.

9. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: In step (1), the ruthenium content in the raw material ruthenium trichloride is 30%~40%, preferably 37%.

10. The efficient preparation method of ruthenium iodide dimer of cymene according to claim 1, characterized in that: The post-processing includes the following steps: cooling the system after the reaction in step (2) to 20~30℃, filtering and collecting the solid product, washing it with deionized water 2~4 times and methanol 1~3 times in sequence, and then drying it at 60~80℃ for 4~8h to obtain p-cymene ruthenium iodide dimer; The amount of deionized water used in a single wash is 1 / 5 to 1 / 3 of the total volume of the reaction system, and the amount of methanol used in a single wash is 1 / 10 to 1 / 5 of the total volume of the reaction system.

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